NM_001063.4:c.1687+2029C>A

Variant names:

• chr3-133772601-C-A
• rs8177297
• NM_001063.4:c.1687+2029C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001063.4(TF):​c.1687+2029C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,192 control chromosomes in the GnomAD database, including 2,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2040 hom., cov: 32)
• Consequence: TF NM_001063.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 3 publications found

Genes affected

TF (HGNC:11740): (transferrin) This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. [provided by RefSeq, Sep 2009]

TF Gene-Disease associations (from GenCC):

• atransferrinemia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	NM_001063.4	MANE Select	c.1687+2029C>A		intron	N/A	NP_001054.2	P02787
	TF	NM_001354703.2		c.1555+2029C>A		intron	N/A	NP_001341632.2
	TF	NM_001354704.2		c.1306+2029C>A		intron	N/A	NP_001341633.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.1687+2029C>A		intron	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.1039+2029C>A		intron	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.700+2029C>A		intron	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21318 AN: 152074 Hom.: 2043 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.157

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21317 AN: 152192 Hom.: 2040 Cov.: 32 AF XY: 0.145 AC XY: 10814 AN XY: 74414

African (AFR) AF: 0.0322 AC: 1336 AN: 41538

American (AMR) AF: 0.195 AC: 2980 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1969 AN: 5166

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1361 AN: 10578

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11199 AN: 67996

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.0767 Hom.: 112

Bravo AF: 0.138

Asia WGS AF: 0.283 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8177297; hg19: chr3-133491445; COSMIC: COSV53918999; COSMIC: COSV53918999;